Shockwaves are continuous single soundwaves generated by a specific soundwave generator, which have a high peak pressure amplitude of up to 100 MPa and a short duration of less than 1 μm. Further, shockwaves can deliver to a specific target area with an energy density in the range of 0.005 mJ/mm2 to 1.0 mJ/mm2.
High-energy extracorporeal shock-wave lithotripsy (ESWL) is a kind of treatment for breaking stones in the kidney and bile duct by applying pressure of 35 MPa to 100 MPa to the target area of the human body. New treatments have been attempted in a variety of fields since such method was first tried. Recently, it has been reported that extracorporeal shock-wave lithotripsy is used in the treatment of musculoskeletal diseases and is useful for anti-inflammatory action and blood flow increase.
Extracellular vesicles are nanoparticles vesicles composed of a bilayer lipid membrane, which have several tens of nanometers to several hundreds of nanometers. Further, they are composed of biologically active substances such as proteins, lipids, and genes. In the past, they were regarded as debris secreted from the cells, but they are now considered clinically meaningful. Therefore, various studies about the extracellular vesicles are actively going on. In particular, exosomes, which are the spherical follicles released by cells, have lots of information about the mother cell protein and DNA, etc. Thus, it has been actively attempted to develop a marker and a sensor to detect cancer using the same as a biomarker. For example, studies have suggested the diagnosis of glioblastoma based on the detection of EGFRVIII genes, a form mutated from extracellular vesicles present in the patient's blood. There are also studies that have confirmed the presence of prostate cancer biomarkers PCA-3 and TMPRSS2:ERG in extracellular vesicles present in the patient's urine through the genomic analysis of extracellular vesicles derived from cancer cells. Further, Korean Patent No.: 10-1704828 discloses a method for diagnosing an inflammatory disease by analyzing the expression level of inflammatory-related disease genes which present in extracellular vesicles in body fluids.
Meanwhile, the present inventors have found, before suggesting the present disclosure, that the production and secretion of extracellular vesicles such as exosomes, ectosomes, microvesicles or apoptotic bodies into which desired target materials are introduced by treating with extracorporeal shockwaves, thereby establishing a method of preparing cells including the target materials in Korean Patent No.: 10-1719569. However, this method confirms that extracellular vesicles produced by extracorporeal shockwave applied to cells are only medium in the transformation process but does not disclose a mechanism of using extracellular vesicles, especially exosomes themselves and a transformation method using the same directly. Compared with cell-based therapies, exosome-based drug deliveries or therapies may have no vascular obstructive effect and may reduce the risk of secondary microvascular thrombosis and the risk of tumor formation. Further, exosomes can be obtained in a large number through a small number of cells. A large number of exosomes obtained as described above have many merits that they are stable, easy to store, do not induce an immune rejection reaction, thereby easily applying in clinical practice. Therefore, there is a need to study cell treatment using exosomes themselves, which is improved compared to cell-mediated therapies.